The article reviews the biochemical, molecular, and physiological roles of poly(ADP-ribosyl)ation (PARylation) and the PARP-1 enzyme. PARylation is a covalent modification that plays crucial roles in various cellular processes, including DNA damage repair, chromatin remodeling, transcription, cell death, and mitotic function. PARP-1, the founding member of the PARP family, catalyzes the synthesis of PAR on target proteins using NAD+ as a donor. The enzyme has a highly conserved structure, including an N-terminal DNA-binding domain, a nuclear localization signal, an automodification domain, and a C-terminal catalytic domain. PARP-1's enzymatic activity is stimulated by various factors, including damaged DNA and protein partners, and it targets itself, histones, and transcription factors for modification. The catabolism of PAR is mediated by PARG, which hydrolyzes PAR to free ADP-ribose. The regulation of PAR levels by PARPs and PARG is critical for maintaining cellular homeostasis. PARP-1 and PARylation are involved in DNA damage detection and repair, where they act as sensors and recruit repair proteins. They also play roles in cell death pathways, where they can promote necrosis or apoptosis, and in chromatin structure regulation, where they modulate the compaction and decondensation of chromatin. Additionally, PARP-1 and PARylation influence transcriptional regulation, insulator function, and mitotic apparatus function. The physiological and pathophysiological implications of PARP-1 and PARylation are discussed, including their roles in genome maintenance, carcinogenesis, aging, inflammatory responses, and neuronal function.The article reviews the biochemical, molecular, and physiological roles of poly(ADP-ribosyl)ation (PARylation) and the PARP-1 enzyme. PARylation is a covalent modification that plays crucial roles in various cellular processes, including DNA damage repair, chromatin remodeling, transcription, cell death, and mitotic function. PARP-1, the founding member of the PARP family, catalyzes the synthesis of PAR on target proteins using NAD+ as a donor. The enzyme has a highly conserved structure, including an N-terminal DNA-binding domain, a nuclear localization signal, an automodification domain, and a C-terminal catalytic domain. PARP-1's enzymatic activity is stimulated by various factors, including damaged DNA and protein partners, and it targets itself, histones, and transcription factors for modification. The catabolism of PAR is mediated by PARG, which hydrolyzes PAR to free ADP-ribose. The regulation of PAR levels by PARPs and PARG is critical for maintaining cellular homeostasis. PARP-1 and PARylation are involved in DNA damage detection and repair, where they act as sensors and recruit repair proteins. They also play roles in cell death pathways, where they can promote necrosis or apoptosis, and in chromatin structure regulation, where they modulate the compaction and decondensation of chromatin. Additionally, PARP-1 and PARylation influence transcriptional regulation, insulator function, and mitotic apparatus function. The physiological and pathophysiological implications of PARP-1 and PARylation are discussed, including their roles in genome maintenance, carcinogenesis, aging, inflammatory responses, and neuronal function.